Rare Case Report of Angiolymphoid Hyperplasia with EosinophiliaRK Belkharoeva, AR Hubail*, NP Tepljuk, OY Olisova, VB Pinegin and VA Koroleva

I.M. Sechenov First Moscow State Medical University, Russian Federation*Corresponding author: AR Hubail, Dermatology Resident, I.M. Sechenov First Moscow State Medical University, Russian Federation, Tel: +7 985 759 85 34; E-mail: dr.amalhubail@gmail.comReceived date: November 27, 2017; Accepted date: January 15, 2018; Published date: January 22, 2018

Copyright: © 2018 Belkharoeva RK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aims and objective: The aim of this study was to assess the clinical and demographic features of a rarecutaneous condition, angiolymphoid hyperplasia with eosinophilia (ALHE), and compare them with those previouslyreported. ALHE is a benign vascular proliferation of unknown etiology and its treatment is unclear.

Methods: A 29 year old woman visited the Hospital of Skin and Venereal diseases for pruritic lesion in the ear.She presented with a reddish papulonodular rash. Laboratory tests showed no abnormalities. She was diagnosedwith ALHE based on clinical, histological, and immunological features. Treatment with injectable prolonged systemicglucocorticoid and topical prednisolone was initiated. The rash and pruritic sensation improved within one week inthe hospital, and the reddish infiltration and nodules had dramatically decreased at the 6 month follow-up.Continuous topical application resulted in no recurrence at the 6 month follow-up.

Results and conclusion: Management of ALHE is still poorly standardized and poorly understood due touncertainties concerning its pathophysiology and development and the small number of available studies.Establishing the final clinical diagnosis is difficult owing to the absence of subjective sensations. ALHE can persistfor years but serious complications like cancer transformation do not occur.

Keywords: Kimura's disease; Angiolymphoid hyperplasia;Eosinophilia; Cutaneous neoplasms

IntroductionAngiolymphoid hyperplasia with eosinophilia (ALHE) is a

vasoproliferative idiopathic condition that represents a reactivehyperplasia of blood vessels with signs of arteriovenous anastomoses[1-3]. It manifests as nodular plaques or papules mostly around thehead and neck, and rarely in other areas, such as the breasts, penis,hands, scrotum, shoulders and oral mucosa. Kimm and Szeto firstdiscovered this disease in 1937 [1], reporting 7 cases of hyperplasticeosonophilic granuloma. In 1948, Kimura et al. [3] described it as anunusual granulomatosis combined with hyperplastic changes in thelymphoid tissue and eosinophilia. It has since been called Kimura’sdisease (KD) [4-11]. However, in 1969, Wells and Whimster [12]presented a case with clinical and morphological characteristics similarto those of KD, calling it subcutaneous ALHE. To date, few studieshave reported that KD and ALHE are different clinical variants of thesame disease, indicating that ALHE is an arteriovenous disease withsecondary inflammation and KD is an inflammatory process withsecondary vascular proliferation [4,5].

Based on the literature, ALHE occurs in women and middle-agedAsian men, and is more common in young women with positiveallergic anamnesis (bronchial asthma, pollinosis and atopic dermatitis)[6,7]. However, its etiology remains unknown.

Case Report

Presenting historyA 29 year old woman visited the Rakhmanova Skin and Venereal

Diseases Hospital of Sechenov First Moscow State Medical Universitybecause of pruritic rashes on the tragus of the outer ear and behind theear present for many years. The rashes were unaccompanied bysubjective sensations.

Based on her past medical history, the first rash appeared 5 yearsprior her visit. The patient did not self-treat or seek medical advice.Since then, the lesions grew slowly, without disturbing the patient orcausing any discomfort. Clinical and biochemical blood tests andgeneral urine analysis did not show any irregularities. Test results for acomplex of hemotransmissive infections were negative. Computedtomography scan of the chest and abdominal ultrasound revealed theabsence of any pathology.

Clinical examinationOn physical examination, multiple papular lesions localized in the

right tragus of the outer ear were noted. These monomorphic papuleswere ~5 mm in diameter, hemispherical in shape, not sharplydemarcated from the surrounding healthy skin, reddish-blue in colorand of solid consistency. The skin integuments outside the lesions werepale pink, clean, and moderately humid. Turgor and elasticity were inaccordance with age. The mucous membranes, hair, and nail plates ofthe hands and feet were not affected. Marked enlargement of thelymph node of up to 2.5 cm was noted posterior to the auricle on thesame side; the skin over the lymph node was unchanged. The

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remaining lymph nodes were not palpable. No other subjectivefindings were noted (Figure 1).

Figure 1: Multiple papular lesions on the patient’s ear onpresentation.

Histopathological investigationsA skin biopsy specimen was obtained, and histopathological

findings were of parakeratosis, acanthosis, spongiosis with theformation of intradermal vesicles with neutrophilic granulocytes andvacuolar degeneration of keratinocytes. The dermis had signs of edemaand moderately marked lymphoid proliferation of small blood vessels,which were small, with round, oval, and irregular nuclei; moreover,both histiocytes and eosinophilic granulocytes were identifiedperivascularly and periglandularly. Perivascular infiltrate consistedmainly of lymphocytes without obvious signs of epidermotropism andeosinophils (Figure 2).

Figure 2: Histology slide from patient’s skin biopsy showingproliferation of small blood vessels in the dermis, perivascularinfiltrate consisting mainly of lymphocytes without obvious signs ofepidermotropism and eosinophils.

Immunohistochemical investigationsImmunohistochemical study revealed mostly positive CD34 and

CD31 reactions of the endothelium in numerous vessels and only a fewwere positive for alpha CD79, indicating the predominance of T-lymphocyte infiltration. The proliferative activity of Ki-67 in theendothelial cells was low. E-cadherin in the spongy areas of alteredepithelial layer was immunoreactive. Thus, no elements of tumorgrowth of stroma fibrosarcoma were detected (Figure 3).

Figure 3: Immunohistochemistry study of CD4+, CD3+ and actinrespectively, showing positive results, indicating predominance ofT-lymphocyte infiltration.

TreatmentBased on the medical history, physical examination, and

pathohistological data, we established a diagnosis of ALHE. Treatmentwas initiated using prolonged systemic glucocorticoid, betamethasonesodium phosphate and betamethasone acetate injectable suspension 30mg/5 mL (6 mg/mL) administered at 1 ml per week for 2 weeks. Theconcomitant therapy included 0.5% topical prednisolone.

The size of the infiltrate was reduced by 60% after in-hospitaladmission and treatment for 1 week. The patient was discharged withrecommendations to continue treatment with prolonged topicaltherapy. Informed consent was obtained on admission.

Follow upAt the 3 month follow-up, there was concern that the lesions might

have relapsed or remained static without improvement, but the lesionssignificantly regressed. At the 6 month follow-up, the lesions regressedby approximately 70% in comparison to the time of presentation(Figure 4).

Citation: Belkharoeva RK, Hubail AR, Tepljuk NP, Olisova OY, Pinegin VB, et al. (2018) Rare Case Report of Angiolymphoid Hyperplasia withEosinophilia. J Dermatol Dis 5: 269. doi:10.4172/2376-0427.1000269

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Figure 4: Lesions at 6 month follow-up showing great improvement.

DiscussionALHE is generally considered a benign reactive lymphoproliferative

process, causing the formation of a localized non-proliferating lesionwith small blood vessels surrounded by white blood cells (lymphocytesand eosinophils). The cause of ALHE is unknown. Existing theorieslink it to injury or insect bites [5].

The diagnosis of ALHE is based on biopsy and clinical presentation.Clinically, it is characterized by small brownish papules, 2-5 mm indiameter, clustered on a background of normal skin surface, with orwithout slight peeling. The rash is frequently localized on the neck andscalp; exposure of regional lymph nodes and salivary glands is alsopossible. The lesions may be pruritic, asymptomatic, or painful.Uncommon symptoms include bleeding and pulsation [8].

Histology results reveal hyperplasia of small blood vessels lined withrounded endothelial cells, with abundant cytoplasm and sometimesatypical nucleus; the vessels are similar to the endothelial venules oflymphoid tissue. The dermis is inflamed with increased vascularity [6].Direct immunofluorescence shows fixation of IgA and IgM and the C3component of the complement in the walls of the skin blood vessels.Complete blood count may show eosinophilia in up to 20% of casesonly. Urinalysis may be also considered because renal disease occurs insome patients with ALHE rarely [5,9].

The differential diagnosis includes pseudolymphomas(lymphoplasia), sinus histiocytosis with massive lymphadenopathy,pyogenic granulomas, hemangiomas, soft tissue tumors, angiosarcoma,Kaposi sarcoma, bacillary angiomatosis, bartonellosis, sarcoidosis,metastatic carcinoma, cutaneous B-cell lymphoma, and otherlymphomas. No unified approach exists for ALHE (KD) treatment.

The treatment depends on the size of the lesion and chronicity. Ifthe lesion is small, observation for 3-6 months is recommended due toa chance of spontaneous regression. If the lesion is large, then surgicalexcision of the tumor tissues is suggested; however, relapses were

observed in most patients who underwent surgery, particularly withincomplete excision. Mohs micrographic surgery with excision of theabnormal vessels has been proven to be very effective. If surgery iscontraindicated, treatment of relapses and resistant disease isperformed by glucocorticosteroid and local radiation therapies (25-30Gy). One study reported that the clinical effect of radiotherapy wasachieved in 74% of their patients. The most commonly used radiationtherapy is pulsed dye laser. Other modes of ALHE treatment includesystemic, intrafocal and topical corticosteroids, electro-dessication,cryotherapy and hormonal therapies. ALHE recurrence was reportedin the literature after discontinuation of hormonal therapy, such asimiquimod ointment [10-15].

Research has shown good insight with treatment using oralpropranolol, with no recurrence reported after its use. Using topicaltimolol is another modality that has been tried with some success.Despite the multiplicity of therapeutic modalities, their real efficacy hasnot been well studied, and frequent recurrences have been noted[10-15].

Prognosis is variable. Even with surgery, approximately 41% failurerate is observed. This condition generally persists for years, butcomplications actually rarely occur and these may includenephropathy [10].

ConclusionWe present a rare cutaneous dermatosis, wherein establishing the

final clinical diagnosis of this disease was difficult owing to the absenceof subjective sensations and overall undisturbed condition despite thepresence of the disease for several years. In the future, patients withthis diagnosis must be constantly followed up by a dermatologist toprevent the transformation process. This article lays the grounds forfuture research, particularly on early detection of the condition as it ismisdiagnosed at first in most cases.

References1. Kim HT, Szeto C (1937) Eosinophilic hyperplastic lymphogranuloma,

comparison with Mikulicz’s disease [in Chinese]. Chin Med J 23: 699-700.2. Аrmstrong WB, Allison G, Pena F, Kim JK (1998) Kimura’s disease: two

case reports and a literature review. Ann. Otol Rhinol Laryngol 107:1066-1071.

3. Kimura’s T, Yoshimura S, Ishikawa E (1948) On the unusual granulationcombined with hyperplastic changes of lymphatic tissues. Trans SocPathol Jpn 37: 179-180.

4. Carlesimo M, Mari E, Tammaro A, Persechino S, Camplone G. (2007)Angiolymphoid hyperplasia with eosinophilia treated with isotretinoin.Eur J Dermatol 17: 554-555.

5. Larroche C, Blétry O (2005) Kimura’s disease. Orphanet Encyclopedia.6. Wolff K, Goldsmith LA, Katz SI, Gilchrest B, Am Paller AS et al. (2012)

Angiolymphoid hyperplasia with eosinophilia and Kimura disease.Fitzpatrick Dermatology in General Medicine, McGraw Hill Medical,USA.

7. Olisova O, Potekaev N (2013) Cutaneous pseudolymphoma. Practice 7:1-138.

8. Isohisa T, Masuda K, Nakai N, Takenaka H, Katoh N (2014)Angiolymphoid hyperplasia with eosinophilia treated successfully withimiquimod. Int J Dermatol 53: e43-e44.

9. Adler BL, Krausz AE, Minuti A, Silverberg JI, Lev-Tov H (2016)Epidemiology and treatment of angiolymphoid hyperplasia witheosinophilia (ALHE): A systematic review. J Am Acad Dermatol74:506-512.

Citation: Belkharoeva RK, Hubail AR, Tepljuk NP, Olisova OY, Pinegin VB, et al. (2018) Rare Case Report of Angiolymphoid Hyperplasia withEosinophilia. J Dermatol Dis 5: 269. doi:10.4172/2376-0427.1000269

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10. Wanat K, James A (2010) Kimura disease: Treatment and medication.Emedicine, Accessed on 21 August 2017.

11. Kohli A, Singh G (2008) Kimura’s disease. JK Sci 10: 149-150.12. Wells GC, Whimster IW (1969) Subcutaneous angiolymphoid

hyperplasia with eosinophilia. Br J Dermatol 81:1-14.13. Ivanov OL (2007) Skin and venereal disease: A Handbook. In: Medicine,

Moscow, pp: 118-119.

14. Horst C, Kapur N (2014) Propranolol: A novel treatment forangiolymphoid hyperplasia with eosinophilia. Clin Exp Dermatol 39:810-812.

15. Chacon AH, Mercer J (2016) Successful management of angiolymphoidhyperplasia with eosinophilia in a split-face trial of topical tacrolimus andtimolol solution. G Ital Dermatol Venereol 15: 436-440.

Citation: Belkharoeva RK, Hubail AR, Tepljuk NP, Olisova OY, Pinegin VB, et al. (2018) Rare Case Report of Angiolymphoid Hyperplasia withEosinophilia. J Dermatol Dis 5: 269. doi:10.4172/2376-0427.1000269

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J Dermatol Dis, an open access journalISSN:2376-0427

Volume 5 • Issue 1 • 1000269